Number of Participants Who Successfully Swallowed Study Medication (Med) on Day 2 [ Time Frame: Day 2 ] [ Designated as safety issue: No ]

The Swallowing Ability Questionnaire was completed on Day 2 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.

Number of Participants Who Successfully Swallowed Study Med on Day 4 [ Time Frame: Day 4 ] [ Designated as safety issue: No ]

The Swallowing Ability Questionnaire was completed on Day 4 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.

Number of Participants Who Successfully Swallowed Study Med on Day 6 [ Time Frame: Day 6 ] [ Designated as safety issue: No ]

The Swallowing Ability Questionnaire was completed on Day 6 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.

Number of Participants Who Successfully Swallowed Study Med on Day 9 [ Time Frame: Day 9 ] [ Designated as safety issue: No ]

The Swallowing Ability Questionnaire was completed on Day 9 after the participant received two matching placebo tablets (excluding marking) following consumption of a low- to moderate-fat meal in pediatric participants aged 10 to 17 years. The questionnaire consisted of five parts: could only swallow study med with help, easy to start swallowing study med, easy to swallow study med, felt like study med got stuck in throat, and had to swallow study med more than once. The number of participants who strongly agreed or agreed in each of the five parts is reported.

Area Under the Curve 0 to Last (AUC 0-last) of Sitagliptin Following Single Administration of Sitagliptin/Metformin XR [ Time Frame: Pre-dose, and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24, 48, and 72 hours post-dose ] [ Designated as safety issue: No ]

In this study, metformin products were withheld 24 hours (hrs) prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hrs post study drug administration. Owing to resumption of therapeutic metformin administration 24 hrs after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax) and area under the curve 0 to 24 hrs (AUC0-24hr). Therefore, metformin arm is not included in this outcome measure.

In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another outcome measure.

In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this outcome measure.

In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Due different units of measure for sitagliptin and metformin, sitagliptin data are presented in another outcome measure.

In this study, metformin products were withheld 24 hours prior to sitagliptin/metformin XR administration and were permitted to re-initiate 24 hours post study drug administration. Owing to resumption of therapeutic metformin administration 24 hours after sitagliptin/metformin XR administration for all participants, metformin pharmacokinetic analyses were restricted to Cmax, Tmax and AUC0-24hr. Therefore, metformin arm is not included in this outcome measure.

Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) ] [ Designated as safety issue: Yes ]

An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered.

Number of Participants Who Experienced an Abnormal Vital Sign Value [ Time Frame: Up to 23 days (including approximately 10 to 14 days after the last dose of study drug) ] [ Designated as safety issue: Yes ]

Number of Participants Who Discontinued Study Drug Due to an AE [ Time Frame: Up to 9 days ] [ Designated as safety issue: Yes ]

An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an IMP, regardless of causal relationship and even if no IMP has been administered.

Original Primary Outcome Measures ICMJE (submitted: March 16, 2012)

Number of participants who experienced at least one adverse event [ Time Frame: Through approximately 10 to 14 days following last dose ] [ Designated as safety issue: Yes ]

Number of participants who experienced at least one abnormal vital sign [ Time Frame: Through approximately 10 to 14 days following last dose ] [ Designated as safety issue: Yes ]

Number of participants who were able to swallow study drug [ Time Frame: Baseline through approximately 10 to 14 days following last dose ] [ Designated as safety issue: No ]

Pharmacokinetic analysis of sitagliptin and metformin: Area under the curve (AUC) 0 to infinity, AUC 0 to last, and AUC 0 to 24 hours [ Time Frame: From Baseline up to 72 hours post-dose ] [ Designated as safety issue: No ]

Matching placebo to fixed dose combination tablet of sitagliptin and metformin. Matching placebo tablets are same size, shape and color as the active product, but do not contain any markings.

Drug: Metformin

Concomitant use of metformin is permitted during the study provided the participant has been receiving a stable metformin dose for at least 12 weeks prior to the dose of study drug. Administration of metformin will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.

Drug: Thyroid hormone

Concomitant use of thyroid hormone (eg, levothyroxine) is permitted during the study provided the participant has been receiving a stable dose for at least 12 weeks prior to study drug administration and is euthyroid as documented by thyroid stimulating hormone testing at prestudy. Administration of thyroid hormone will be withheld for 24 hours prior to study drug administration and for 24 hours postdose.

Study Arm (s)

Experimental: Sitagliptin/metformin XR followed by placebo

Day 1 (Period 1): participants will receive a single dose of two sitagliptin/metformin XR tablets with a low- to moderate-fat meal (breakfast). Days 2-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.

Interventions:

Drug: Sitagliptin/metformin XR

Drug: Placebo

Drug: Metformin

Drug: Thyroid hormone

Placebo Comparator: Placebo only

Days 1-4 (Period 1): participants will receive a single dose of two matching placebo tablets. Days 5-9 (Period 2): participants will receive a single dose of two matching placebo tablets with the evening meal.

Interventions:

Drug: Placebo

Drug: Metformin

Drug: Thyroid hormone

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Enrollment ICMJE

25

Completion Date

April 2014

Primary Completion Date

April 2014 (final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Female participant of reproductive potential must not be pregnant and agrees to use (and/or have their partner use) two acceptable methods of birth control

T2DM diagnosed by American Diabetes Association criteria

No clinically significant abnormality on electrocardiogram

No clinical or laboratory evidence to indicate a diagnosis of type 1 diabetes

Unable to refrain from or anticipates the use of any medication (with the exception of metformin and thyroid hormone) from approximately 2 weeks before the first dose of study drug through the poststudy visit